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    Autoantibody Biomarker Discovery

    H-Pylori – Parkinson’s Disease Study

  • Study Design:

    • Investigate the association of H-pylori in PD patients: 30 H. pylori-seropositive PD samples were designated as case and 30 age- and gender- matched H. pylori-seronegative PD samples were used as controls
  • Results:

    • Study identified 13 significant autoantibodies based on ranking using a penetrance fold change method.
    • Among elevated autoantibodies in H. pylori-seropositive PD, NFIA, PDGFB and eIFA3 are essential proteins involved in neurological function.
  • Published study:

    Augmentation of Autoantibodies by Helicobacter pylori in Parkinson’s Disease Patients May Be Linked to Greater Severity

    Fold changes between H. pylori-seropositive PD samples (Case) and H. pylori-seronegative (Control) groups for autoantibodies showing higher activity in the case group.

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    Drug Companion Diagnostics

    Checkpoint Inhibitor Melanoma Trial

  • Study Design:

    • Patients with histologically confirmed stage III/IV metastatic melanoma received intralesional BCG injection followed by up to four cycles of intravenous ipilimumab (anti-CTLA-4). (ClinicalTrials.gov number NCT01838200)
    • Three time points pre-BCG, post-BCG and Post-ipilimumab were considered for autoantibody profiling
    • Patients enrolled for check point inhibitor clinical trails have known auto-immune symptoms pre-treatment
    • BCG-vaccine treatment boosts such broad non-specific auto-immune profile which acts as checkpoint in this study
    • Five patients considered for the study but discontinued as the two patients receiving the escalation dose of BCG developed high-grade immune-related adverse events (irAEs) typical of ipilimumab monotherapy
  • Results:

    • Autoantibody titer were measured for five patients but two patients withh irAEs showed increases in the repertoire of autoantibodies directed against both self- and cancer antigens
    • Induced autoantibodies were detected at time points that preceded the development of symptomatic toxicity
    • Measuring autoantibody responses may provide an early means for identifying patients at risk from developing severe irAEs during cancer immunotherapy
    • Patients treated with immunotherapy develop irAEs that resemble autoimmune disease, autoantibody repertoire of all recruited patients to characterize their serological responses as part of our broader immune-monitoring approach
  • Published study:

    Autoantibodies May Predict Immune-Related Toxicity: Results from a Phase I Study of Intralesional Bacillus Calmette-Guérin followed by Ipilimumab in Patients with Advanced Metastatic Melanoma

     

    Intralesional bacillus Calmette–Guérin (BCG) followed by ipilimumab phase I trial treatment schedule. Dn, day n; Ipi, ipilimumab.

     

    Clinical timelines for all patients, including comparative size-proportional pie-charts representing the number of antigens towards which antibody titers were detected. Timelines are separated by patients who did not develop high-grade irAEs (A) versus those who did (B).

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    Protein Interaction Assays

    DNA-Protein Interaction Study

  • Study Design:

    • p53 microarray printed onto a neutravidin-derivatised dextran hydrogel surface probed with Cy3-labelled GADD45 duplex oligo
  • Results:

    • Quantitative parallel thermodynamic analysis revealed previously unknown functional effects of mutation on p53 protein-DNA interaction
    • Differential DNA binding activity of p53 mutant proteins
    • Quantitative analysis unravels mechanistic differences between ‘loss of function’ mutations
  • Published study:

    Functional protein microarrays for parallel characterisation of p53 mutants

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